1.Risk factors of Crohn′s disease-related gastrointestinal stenosis: a single-center retrospective study
Shanbing YANG ; Shuwen DU ; Limin ZHANG ; Kangmei JIA ; Xiaojuan LU ; Shu LI ; Xin FAN ; Yan JIA ; Peng JIN ; Xinyan YANG ; Jiheng WANG
Chinese Journal of Digestion 2020;40(9):601-605
Objective:To investigate the risk factors of Crohn′s disease (CD)-related gastrointestinal stenosis, and to summarize and analyze the corresponding treatments.Methods:From January 2010 to December 2018, 122 patients diagnosed with CD and hospitalized in the Seventh Medical Center, PLA General Hospital were selected including 72 patients in gastrointestinal stenosis group and 50 patients in non-gastrointestinal stenosis group. The gender, age of onset, course of disease, location of lesions involved (Montreal classification), disease activity, extraintestinal manifestations, application of therapeutic drugs, and complications were compared between the two groups. The treatment of CD patients with gastrointestinal stenosis was analyzed. Multivariate logistic regression was used to analyze the risk factors of CD patients with gastrointestinal stenosis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The age of onset of patients in gastrointestinal stenosis group was older than that in non-gastrointestinal stenosis group ((37.6±15.1) years old vs. (30.8±14.7) years old), and course of disease was longer than that of non-gastrointestinal stenosis group (72 months, 11 to 492 months vs. 45 months, 3 to 240 months); and the differences were statistically significant ( t=-2.044, Z=-2.770; P=0.018, 0.006). The proportion of patients with ileum involvement of the gastrointestinal stenosis group was lower than that of the non-gastrointestinal stenosis group (69.4%, 50/72 vs. 86.0%, 43/50), and the proportion of severe patients was higher than that of the non-gastrointestinal stenosis group (15.3%, 11/72 vs. 4.0%, 2/50); and the differences were statistically significant ( χ2=4.463 and 3.942, P=0.035 and 0.047). There were no significant differences in gender, use of therapeutic drugs, extraintestinal manifestations, application of therapeutic drugs or the incidence of complications between the patients of two groups (all P>0.05). The results of multivariate logistic regression showed that the age of onset and course of disease were risk factors of CD-related gastrointestinal stenosis ( β=0.028, odds ratio ( OR)=1.028, 95% confidence interval ( CI) 1.000 to 1.056, P=0.046; β=0.008, OR=1.008, 95% CI 1.002 to 1.015, P=0.013). Further stratified analysis revealed that the incidence rates of CD-related gastrointestinal stenosis in patients with age of onset over 40 years old and course of disease more than five years were higher than those of patients with age of onset less than 40 years old and course of disease less than five years (76.3%, 29/38 vs. 51.2%, 43/84; 68.4%, 39/57 vs. 50.8%, 33/65), and the differences were statistically significant ( OR=3.072, 95% CI 1.298 to 7.272, P=0.009; OR=2.101, 95% CI 1.002 to 4.406, P=0.048). Among the 72 CD patients with gastrointestinal stenosis, 15 cases (20.8%) were treated with medicine and nutrition, without endoscopic or surgical treatment. Fifty-two patients (72.2%) underwent surgical treatment, among them six patients (11.5%) received twice surgery, the interval between the two operations was 46 months (1 to 204 months), and eight patients (15.4%) had postoperative complications. Twenty-one patients (29.2%) were treated with endoscopic dilatation, and no complications occurred after surgery. Five patients (23.8%) underwent surgical treatment during the follow-up period. Conclusions:The age of onset over 40 years old and the course of disease more than five years are the risk factors of CD-related gastrointestinal stenosis. Individualized medical treatment is the basis for the treatment of CD-related gastrointestinal stenosis. Surgery is still the main treatment. The endoscopic treatment is safety and can delay or avoid surgery to a certain extent.
2.Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction
Xinhao TANG ; Bowen CHU ; Yuanyuan QIN ; Yeling LIU ; Xinyan SHU ; Mianhua WU ; Gang YIN ; Jianguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):176-185
In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.